As his formal training has been in clinical neurology, Dr. Slevin's laboratory has approached the study of the brain and aging from the orientation of disease entities. For the last several years his focus has been directed toward aberrant neuronal plasticity, as exemplified by the epilepsies, and neurodegenerative diseases, especially Parkinson's disease (PD).

To better understand and treat human epilepsy, it is important to understand not only the expression of individual seizures but the development of a lasting seizure-prone state, i.e., epileptogenesis. Inroads to an understanding of this circumstance may be possible through study of the kindling phenomenon, Dr. Slevin's basic research focus in epilepsy. His research in the biochemistry of kindling, in collaboration with Drs. TC Vanaman and SW Whiteheart, has centered on the role of (1) excitatory amino acid neurotransmission and (2) second messenger systems, including their target enzymes which regulate protein phosphorylation. In the past, Dr. Slevin's laboratory has studied protein kinase C, CaM Kinase II, and phosphoprotein phosphatase 2A. More recently, work has centered on the study of the regulation of docking and fusion proteins (e.g., NSF, SNAPS) involved in excitation-secretion coupling. In this work, substantial use is made of immunoassay procedures, including site-specific mutagenesis of proteins of interest. Other typical biochemical procedures include electrophoretic techniques, standard enzyme assays, and affinity chromatography. Other experiments use the in vitro hippocampal slice preparation and synaptosomes. These studies utilize HPLC, coupled enzyme kinetic and receptor-binding techniques. The epilepsy studies also introduce students to techniques of animal surgery and use of electrophysiologic instrumentation for kindling.

Studies of PD are more clinically oriented and include (1) Phase II and Phase III studies of antiparkinson medications and (2)motor/behavioral studies administered before and after pallidotomy and thalamic stimulation surgical procedures. Another component of these investigations includes a study of the normal evolution of movement with aging in a cohort of human volunteers. These individuals, intensely scrutinized under the aegis of the Sanders Brown Center on Aging, have agreed to donate their brain at death. In collaboration with Drs. Greg Gerhardt and Don Gash, accepted behavioral measures of movement (UPDRS - unified PD rating scale)are being compared in these volunteers (as well as in PD patients) with an automated movement analysis system, that Dr. Gash uses in studies of animal models of PD. Techniques are also being developed to study movement in this volunteer group using functional magnetic resonance imaging. Lastly, upon their death, human volunteers will have dopamine/DA metabolites measured in several brain regions and cell counts of substantia nigra both of which will be compared to their motor function in life.